Monoclonal gammopathy is a collective concept that combines a number of diseases, the basis of which is the violation of the efficiency of B-lymphocytes, leading to persistent pathological secretions of one clone of immunoglobulins or their constituent chains.
Benign and malignant nature of the disease
So, monoclonal gammopathy can be benign when clonal cell populations that secrete abnormal immunoglobulins do not show a tendency to uncontrolled reproduction and growth or to a chaotic increase in the production of abnormal proteins.
Pathology can also be malignant in nature, when clonal populations producing an abnormal protein are prone to uncontrolled continuous growth, and at the same time reproduction. As a result, the secretion of this protein usually increases.
Malignant forms of monoclonal gammopathy include, for example, Waldenstrom macroglobulinemia, lung chain disease, etc. The malignant form of the disease is generally less sensitive to chemotherapy compared with most other hemoblastoses.
Causes of pathology
The incidence of this disease increases with age (from one percent in people who are 25 years old, to four percent in people over seventy years old). Monoclonal gammopathy is encountered in combination with other pathologies in which antibodies are produced as the cause of M-protein production, which are formed in large quantities in response to a prolonged antigenic stimulus.
It is worth noting that benign forms of monoclonal gammopathy often develop as a consequence of chronic over stimulation. The latter just leads to increased reproduction of some clones of plasma cells. For example, benign gammopathies, which are observed after bone marrow transplantation, have exactly this character. Much less often, this is recorded immediately after a tissue transplant or in the presence of some chronic infections.
Symptoms
Monoclonal gammopathy is often asymptomatic in humans, although peripheral neuropathies can also occur. Despite the fact that most examples of the disease turn out to be benign, in 25 percent of cases this disease can progress to B-cell tumors, and also to myeloma or to macroglobulinemia.
Symptoms of monoclonal gammopathy should not be ignored.
Diagnostics
Serum immunoglobulin content is assessed by electrophoresis. Immunoglobulins can move in an electric field at different speeds and form a fairly wide peak in the gamma-globulin zone. With the development of monoclonal gammopathy (ICD-10 code - D47.2), the serum content of gamma globulins usually increases in humans, and an acute peak, called the M-gradient, is detected on the electrophoregram in this area. Less often, it can appear in the zone of beta or alpha globulins. The sensitivity threshold of this method is five grams per liter. The monoclonal form of the M-gradient is confirmed by the identification of one type of heavy and light chains during immunoelectrophoresis. Thus, the M-gradient is quantified (by electrophoresis) and qualitatively (by immunoelectrophoresis).
In the event that the monoclonal nature of the secretion has been proven, then in the future it is reasonable to use only electrophoresis. The magnitude of the M-gradient reports the mass of the tumor. The M-gradient acts as a reliable, but specific for a mass examination, tumor marker. It is found not only in monoclonal gammopathies, but also with various lymphoproliferative pathologies. For example, this is observed if the patient has chronic lymphocytic leukemia and cell lymphoma. It is also fixed against the background of malignant neoplasms in the form of chronic myeloid leukemia, breast and colon cancer, and in addition, against the background of a number of autoimmune pathologies (rheumatoid arthritis, myasthenia gravis, autoimmune hemolytic anemia with cold antibodies). And also with other diseases (cirrhosis of the liver, sarcoidosis, parasitic diseases, gangrenous pyoderma, Gaucher disease).
A rare skin disease called Gotgron's scleromyxedema is also usually accompanied by monoclonal gammopathy. With this ailment in the dermis, a positively charged immunoglobulin that carries lambda chains can be deposited. It is possible that these antibodies can be directed against some elements of the dermis.
The nature of the M-gradient with different gammopathies is not the same. It represents normal immunoglobulins, abnormal or their fragments. The secretion of individual chains is not excluded: light or heavy. In twenty percent of cases, a myeloma afflicts only the light chains that appear in the urine as Jones protein. In some plasma cell tumors (in particular, solitary bone and soft tissue plasmacytomas), monoclonal protein is secreted in less than a third of all cases.
In the process of diagnosis, doctors note that the frequency of immunoglobulin secretion in the presence of a myeloma is proportional to their normal serum content.
Treatment
Therapy of monoclonal gammopathy (according to ICD-10 ailment is assigned the code D47.2) is usually not required, however, given the increased risk of hemoblastoses, patients with this paraproteinemia should be examined regularly. In 47 percent of patients, paraproteinemia can persist for life (but does not cause death). Among sixteen percent of patients, myeloma develops, and in ten percent, the level of paraprotein can increase to values that exceed three grams.
It is also worth noting that three percent of patients develop primary amyloidosis along with Waldenstrom macroglobulinemia, and the same number of patients have other hemoblastoses. Hemoblastoses can develop in seventeen percent of patients after ten years. They develop in 33 percent twenty years immediately after the diagnosis of benign monoclonal gammopathy. Sometimes patients undergo chemotherapy as part of the treatment.
Thus, the primary benign, chronic and asymptomatic condition does not require special treatment for monoclonal gammopathy. But patients need continuous monitoring of the amount of monoclonal immunoglobulin in the blood. That is, all treatment in this case comes down to waiting and observing.
Monoclonal gammopathy of unknown origin
Such gammopathy is often characterized by a potentially malignant tumor of the blood system. The following are the features of this type of pathology:
- With an unclear genesis, the patient may have a benign condition that will be precancerous.
- The risks of pathology transition into a tumor depend on the properties of the quantity and type of produced paraprotein, and in addition, on the ratio of heavy and light chains.
- The condition can occur as a result of mutations of B-lymphocytes, which are cells that normally produce immunoglobulins, that is, proteins that protect against infections.
- As a rule, after twenty years, gammopathy of unknown origin can pass into the tumor in forty percent of patients.
- This type of gammopathy is never treated with chemotherapy.
Characterization and features of gammopathy, characterized by an unclear genesis
So, we are talking about a biochemical state when an abnormal M-protein is in the blood, which is an irregular fragment of immunoglobulin or its light chain, which is synthesized by one line of plasma bone marrow cells. It is called wrong, since it does not perform any functions that are useful to the body, acting as a marriage in protein production. In a normal state, its concentration in the blood should be minimal.
In most situations, the level of M-protein is low and does not increase over time. But in some situations, it can critically increase, passing into multiple myeloma or other monoclonal gammopathies.
The pathology, which is distinguished by an unclear genesis, is characterized by a slow division of the plasmocyte clone and the release of M-protein in a low amount. Also, against the background of this disease, there are no signs of multiple myeloma, AL-amyloidosis, or other lymphoproliferative ailments.
The frequency of this pathology in the population is about one percent and grows, as a rule, with age. After fifty years, the disease is found in three percent of the population, and among men who are over eighty, one in twelve. Monoclonal gammopathies of uncertain value account for sixty percent of all pathologies of this kind.
Causes
The reasons for this form of gammopathy, as the name implies, are unfortunately unclear. Only the following risk factors are known:
- First of all, this is age, since the larger it is, the higher the probability of developing an ailment.
- This disease mainly affects males.
- Contact with pesticides, that is, agricultural workers, is especially at risk.
- The presence of multiple myeloma or monoclonal gammaptia, characterized by an unclear genesis among close and direct relatives.
To date, it is not precisely established, as a result of which a tumor forms. There is a working hypothesis about a sequential change in genes that encode the formation of immunoglobulin and the appearance of M-protein. Directly between monoclonal gammopathies and multiple myeloma lies a long way of genetic rearrangement in the plasma cell. Pathology with an unclear genesis involves one line of B-lymphocytes, which produce a larger amount of M-protein. Multiple myeloma is a clone of tumor cells, which is initially located only in the bones, and then spreads to other organs.
Pathology classification
Monoclonal gammopathy of unknown origin in medicine is divided into the following variations:
- Lymphoplasmacytic gammopathy, which can rarely go into multiple myeloma, but can transform into macroglobulinemia or other non-Hodgkin’s lymphomas.
- Plasmacytic gammopathy, which is a clonal proliferation of plasma cells.
Diagnostics
As part of a study of monoclonal gammopathy of uncertain MGUS and laboratory tests, patients must go through the following procedures:
- Obligatory delivery of a general blood test in order to detect reduced hemoglobin.
- Kidney sampling. Creatinine is generally studied in patients to evaluate renal function.
- The study of blood microelements, namely, calcium is analyzed, which is an indicator of the destruction of bone tissue.
- Conducting electrophoresis of blood proteins along with immunofixation of proteins.
- Determination of immunoglobulins in the blood.
- Establishment of free light chains in the blood.
- Determining the amount of beta-2-microglobulin.
Instrumental examinations
As instrumental studies, attention is paid to the following procedures:
- Thus, an X-ray of the skeleton bones is performed on a study of the spine, skull, pelvic bones, femoral and knee joints, and so on.
- Performing magnetic resonance imaging, which is the gold standard in the diagnosis of bone changes in monoclonal gammopathies. It is worth noting that in case of pain in any of the bones, magnetic resonance imaging is required.
- Computed tomography is primarily aimed at the early detection of other blood tumors into which this disease can pass.
- Perform sternal puncture or trepanobiopsy. This procedure is necessary if there is an abnormal kappa lambda index or one of the symptoms.
- Densitometry, that is, an assessment of bone density.
How is monoclonal gammopathy of unknown origin treated? Such a pathology does not require treatment. However, sometimes this state of "incomplete health" turns into a more serious disease, so you need to be regularly observed by a hematologist. It may take years of observation before such a transition occurs.
In children
The pathology under consideration is a localized and, as a rule, self-limiting disease among children who are between the ages of five and ten years, and young adult patients up to thirty. Often, organs affected by monoclonal gammopathy in children are bones, and in addition, the lungs. Bone damage often prevails, but endocrine gland involvement is often observed. This disease is extremely unfavorable in children who are under the age of two years.
Back pain
Back pain with monoclonal gammopathy often occurs in those patients who have a tumor growth in the vertebra or in the region of the paravertebral soft tissues. Similar discomfort can also occur if there are signs of compression of the roots or spinal cord. In the framework of the study, in order to eliminate discomfort, patients undergo magnetic resonance imaging to detect damage to the spinal cord, and in addition, to assess the severity of the pathological condition of the spine.
Reviews of doctors and patients
In reviews regarding the support of patients with this disease, doctors write that electrophoresis of protein fractions is an indispensable tool for screening and diagnosing malignant forms of monoclonal gammopathies associated with immunoproliferative diseases.
In the comments of patients about this disease, it is noted that it is very important to conduct its early diagnosis and prevention. Experts emphasize that the widespread use of biochemical analyzes and electrophoresis of blood has led to the possibility of early detection of the disease.
Is it possible to live with monoclonal gammopathy? According to patients, if a person finds this disease, as well as after confirming such a diagnosis according to modern requirements, it is recommended to adhere to a certain specialist observation algorithm. In the absence of complaints from the patient during the first year, a study of the amount of paraprotein is carried out, which must be done every three months. And magnetic resonance imaging, according to patients, is done every six months. If an increase in paraprotein is not detected, then further studies are performed every twelve months.
Thus, monoclonal gammopathies (and they are also called immunoglobulinopathies or paraproteinemia) are a heterogeneous category of diseases characterized by proliferation of lymphoid cells that secrete immunoglobulins. The main distinguishing feature of such diseases is the production of monoclonal immunoglobulin, which is determined in blood serum or in urine.